Opioid treatment has been shown to have profound neuroimmune effects. Morphine causes generalized suppression of immune function leading to an increased incidence of opportunistic disease and infection and has been shown to alter levels of receptors, such as the NMDA receptor, leading to neurochemical changes within the brain. These neurochemical changes have been implicated in the development of tolerance and dependence to the analgesic, immuno-suppressive and addictive properties of opioids. While most neuroimmune studies have traditionally used passive treatment paradigms (injection or subcutaneous pellet), addiction studies of opioids generally utilize the self-administration paradigm where animals must work to receive drug and are therefore "contingently-dosed." Although clinically relevant to a drug-abusing population, little work has been done to study the neuroimmune effects of self-administered opioids. To test the hypothesis that neuroimmune changes in animals passively administered opioids may differ during self-administration, the experiments proposed here will look at the effects of opioids in animals that are self- administering morphine and "yoked" animals that receive morphine passively. The specific aims of this proposal are to: 1) characterize immune changes by looking at cellular and humoral immune function, 2) measure corticosterone levels to determine hypothalamic-pituitary axis response, 3) determine changes in NMDA receptor subunit regulation and, 4) examine neurochemical changes by analyzing NMDA receptor-mediated dopamine release in relevant brain regions during contingent and non-contingent opioid treatment.